Exposure to ozone (O3) causes focal lesions throughout the lung: alters airway function, and increases airway reactivity. These local effects are modulated by the magnitude of ozonolysis, the capacity of the antioxidant system, and the extent of mediator metabolism. The outcome of O3 exposure can be assessed by monitoring changes in airway structure and function. However, because the primary site of O3-induced injury is located in the lung periphery: and peripheral airways account for only a fraction of the total airway resistance, it is unlikely that conventional measurements of pulmonary function could reliably detect the initial changes in peripheral airways caused by O3. Thus, a bronchoscope will be used to study canine peripheral airway responses to O3. The relationship between acute O3- induced changes in peripheral airway morphology and transient changes in peripheral airway function and reactivity will be examined. These initial O3-induced events will be followed through time to document the progressive changes in peripheral airway and vascular structure and physiology that occur during subacute exposures to low concentrations of O3. Three hypotheses will be tested: 1) O3-induced injury is heterogeneously distributed and associated with local changes in peripheral airway function and reactivity, 2) A functional transition from a muscarinic-dependent to a muscarinic-independent mechanism occurs during prolonged periods of exposure to low concentrations of O3 and contributes to the development of airway hyperreactivity, and 3) Local antioxidant and media for concentrations determine the magnitude of O3-induced injury and modulate local changes in peripheral airway function and reactivity. In testing these hypotheses, the location and magnitude of O3-induced injury, bronchovascular hyperpermeability, and inflammation will be examined in relation to local changes in peripheral airway function and reactivity. Local concentrations of lipid peroxidation products, antioxidants, and biochemical mediators associated with O3-induced changes in peripheral airway function and reactivity will be determined using low volume bronchial lavage. Finally, anti-inflammatory drugs and antioxidant supplementation will be used in an attempt to reduce or eliminate oxidant- induced injury. The effects of these interventions on peripheral airway morphology, function, and reactivity will be documented, and should provide insights into the underlying mechanisms that mediate the extent of O3-induced damage and the subsequent changes that occur in peripheral airway function and reactivity.